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Hepatitis C Virus and Atherosclerosis in Patients With Type 2 Diabetes
To the Editor: Epidemiologic studies have suggested possible atherogenic roles for such pathogens as Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus.1 However, few data are available on the relation between hepatitis C virus (HCV) infection and atherosclerosis.2 With the availability of more reliable assays, HCV infection is emerging as an extremely common and insidiously progressive disease. The prevalence of antibodies to HCV (anti-HCV) in patients with diabetes was reported to be higher than in healthy blood donors.3 We therefore investigated whether HCV might have a pathogenic effect in atherosclerosis among patients with type 2 diabetes.
Methods
Blood from 210 consecutive patients with type 2 diabetes who underwent carotid ultrasonography as a screening procedure was tested for anti-HCV using a commercial second-generation enzyme-linked immunosorbent assay (Dinabot Co Ltd, Tokyo, Japan). Carotid ultrasonography, which is used increasingly in clinical research concerning the pathophysiology of atherosclerosis, was performed as previously described.4 We defined a plaque as a distinct area with an intima-media thickness (IMT) that visually appeared thicker than that of neighboring sites, and calculated a plaque score by totaling the maximum thickness of all plaques measured in millimeters on the near and far walls of the vessels. Our study had approval from a local institutional review board, and all patients provided oral informed consent. Patients with a positive HCV result were notified of this finding.
Results
Of the 210 diabetic patients, 31 (14.8%) were positive for anti-HCV. Most clinical characteristics of patients with (n = 31) and without (n = 179) HCV infection were not statistically different (mean [SD] age, 65.6 [6.1] vs 65.2 [6.8] years; BMI, 22.7 [3.2] vs 23.3 [3.7]; duration of diabetes, 10.4 [8.4] vs 9.0 [9.0] years; glycohemoglobin level, 7.7% [1.7%] vs 7.4% [1.1%]; C-reactive protein level, 0.20 [0.08] vs 0.18 [0.07] mg/dL; presence of hypertension, 48.4% vs 41.9%; history of cigarette smoking, 38.7% vs 30.7%). However, significantly fewer patients with HCV infection had hyperlipidemia (32.3% vs 43.0%, P = .01). Mean (SD) IMT was significantly greater in patients with anti-HCV (1.03 mm [0.25 mm] vs 0.94 mm [0.23 mm], P = .04), as was median (interquartile range) plaque score (4.78 [2.48-7.19] vs 1.59 [0-4.57], P<.001 by the Mann-Whitney U test). Presence of any plaque was also significantly higher in those with anti-HCV (P<.001 by the Fisher exact test). Seropositivity for HCV was an independent risk factor ( = .358, P<.001) for atherosclerosis (plaque score) after adjustment for age, hypertension, hyperlipidemia, smoking history, and glycohemoglobin level.
Comment
Despite our small sample size, we found a statistically significant association between HCV positivity and ultrasonographic evidence of carotid atherosclerosis among patients with type 2 diabetes. Prospective, large-scale studies are needed to assess the association between HCV infection and atherosclerosis. Clinical studies have shown that serum concentrations of hepatocyte growth factor (HGF) and interleukin 6 (IL-6) are increased in patients with chronic hepatitis C infection, most likely as a result of HCV-induced inflammation.5 Although we did not measure concentrations of HGF or IL-6, our results are compatible with associations demonstrated between increased serum HGF and IL-6 concentrations and atherosclerosis.6
Michiaki Fukui, MD;
Yoshihiro Kitagawa, MD
Department of Endocrinology and Hematology
Osaka General Hospital of West Japan Railway Company
Osaka, Japan
Naoto Nakamura, MD;
Toshikazu Yoshikawa, MD
First Department of Internal Medicine
Kyoto Prefectural University of Medicine
Kyoto, Japan
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2. Ishizaka N, Ishizaka Y, Takahashi E, et al. Association between hepatitis C virus seropositivity, carotid-artery plaque, and intima-media thickening. Lancet. 2002;359:133-135.
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3. Simo R, Hernandez C, Genesca J, Jardi R, Mesa J. High prevalence of hepatitis C virus infection in diabetic patients. Diabetes Care. 1996;19:998-1000.
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4. Handa N, Matsumoto M, Maeda H, et al. Ultrasonic evaluation of early carotid atherosclerosis. Stroke. 1990;21:1567-1572.
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5. Malaguarnera M, Di Fazio I, Romeo MA, Restuccia S, Laurino A, Trovato BA. Elevation of interleukin 6 levels in patients with chronic hepatitis due to hepatitis C virus. J Gastroenterol. 1997;32:211-215.
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6. Nishimura M, Ushiyama M, Ohtsuka K, et al. Serum hepatocyte growth factor as a possible indicator of vascular lesions. J Clin Endocrinol Metab. 1999;84:2475-2480.
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Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.
JAMA. 2003;289:1245-1246.
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